Host acid signal controls Salmonella flagella biogenesis through CadC-YdiV axis
Weiwei Wang,
Yingying Yue,
Min Zhang,
Nannan Song,
Haihong Jia,
Yuanji Dai,
Fengyu Zhang,
Cuiling Li,
Bingqing Li
Affiliations
Weiwei Wang
Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
Yingying Yue
Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
Min Zhang
Department of Pathogen Biology, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
Nannan Song
Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
Haihong Jia
Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
Yuanji Dai
Department of Pathogen Biology, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
Fengyu Zhang
State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Qingdao, China
Cuiling Li
Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
Bingqing Li
Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
Upon entering host cells, Salmonella quickly turns off flagella biogenesis to avoid recognition by the host immune system. However, it is not clear which host signal(s) Salmonella senses to initiate flagellum control. Here, we demonstrate that the acid signal can suppress flagella synthesis and motility of Salmonella, and this occurs after the transcription of master flagellar gene flhDC and depends on the anti-FlhDC factor YdiV. YdiV expression is activated after acid treatment. A global screen with ydiV promoter DNA and total protein from acid-treated Salmonella revealed a novel regulator of YdiV, the acid-related transcription factor CadC. Further studies showed that CadCC, the DNA binding domain of CadC, directly binds to a 33 nt region of the ydiV promoter with a 0.2 μM KD affinity. Furthermore, CadC could separate H-NS-ydiV promoter DNA complex to form CadC-DNA complex at a low concentration. Structural simulation and mutagenesis assays revealed that H43 and W106 of CadC are essential for ydiV promoter binding. No acid-induced flagellum control phenotype was observed in cadC mutant or ydiV mutant strains, suggesting that flagellum control during acid adaption is dependent on CadC and YdiV. The intracellular survival ability of cadC mutant strain decreased significantly compared with WT strain while the flagellin expression could not be effectively controlled in the cadC mutant strain when surviving within host cells. Together, our results demonstrated that acid stress acts as an important host signal to trigger Salmonella flagellum control through the CadC-YdiV-FlhDC axis, allowing Salmonella to sense a hostile environment and regulate flagellar synthesis during infection.
